Akt is selectively activated in NSCLC tissues vs. surrounding lung tissues and confers a poor prognosis for patients with NSCLC. Although no Akt inhibitors exist, other inhibitors of the PI3K/Akt/mTOR pathway are avialable for clinical testing. A series of protocols utilizing pathway inhibitors used either as single agents or in combination with other standard chemotherapies has been put forward in the approval processes that are required to open protocols at the Clinical Research Center and at the National Navlal Medical Center. Currently, there is a Phase I trial of nelfinavir in subjects with relapsed for refractory solid tumors that is open at the Clinical Research Center. This protocol is based on our preclinical studies that showed that nelfinavir is an effective anti-cancer agent in vitro and in vivo that works through multiple mechanisms including Akt inhibition and the induction of apoptosis, ER stress and autophagy.